Endotoxin preconditioning protects neurones from in vitro ischemia: Role of endogenous IL-1β and TNF-α

We have examined whether changes in the expression of several inflammatory factors mediate the neuroprotective action of LPS preconditioning on cerebellar granule neurones (CGN) exposed to the mitochondrial toxin 3-nitropropionic acid (3-NP), chosen as an in vitro ischemic model. CGN were either directly pre-treated with LPS or indirectly by exposure to conditioned medium (CM) from LPS-treated mixed glial cultures obtained from wild type or IL-1β-knock out mice. Following this pre-treatment CGN were incubated with 3-NP and cell viability assessed. Our results show that LPS preconditioning in neurones, promotes neuronal survival against 3-NP-induced cell death and that endogenous TNF-α is a critical mediator for the neuroprotective actions of LPS independently of the presence of endogenous IL-1β after 3-NP exposure.